Article
Andrology
Junaid Kashir, Bhavesh Mistry, Maha Adel Gumssani, Muhammad Rajab, Reema Abu-Dawas, Falah AlMohanna, Michail Nomikos, Celine Jones, Raed Abu-Dawud, Nadya Al-Yacoub, Kevin Coward, F. Anthony Lai, Abdullah M. Assiri
Summary: The study shows that with advancing male age, levels and variability of PLC zeta protein and mRNA in sperm decrease. There are also changes in the localization patterns of PLC zeta in sperm from older male mice.
ASIAN JOURNAL OF ANDROLOGY
(2021)
Review
Chemistry, Medicinal
Haia M. R. Abdulsamad, Zoha F. F. Murtaza, Hessa M. M. AlMuhairi, Wjdan S. S. Bafleh, Salma A. A. AlMansoori, Shaikha A. A. AlQubaisi, Hamdan Hamdan, Junaid Kashir
Summary: Oocyte activation, driven by calcium oscillations mainly regulated by PLC zeta, is crucial for mammalian fertilization and embryogenesis. Failure of calcium release or defects in related mechanisms can lead to infertility in humans. Exploration of PLC zeta and its patterns in human sperm may offer potential for diagnosing and treating human fertility issues. This review provides a comprehensive update on the clinical associations between calcium release, PLC zeta, oocyte activation, and human fertility, discussing their implications in defective embryogenesis and infertility treatments.
Review
Obstetrics & Gynecology
Junaid Kashir, Durga Ganesh, Celine Jones, Kevin Coward
Summary: Oocyte activation deficiency (OAD) is a major cause of ICSI cycle failure. Assisted oocyte activation (AOA) is a method that artificially increases the levels of intracytoplasmic calcium ions (Ca2+) through mechanical, electrical, and/or chemical stimuli. However, the safety and efficacy of AOA are still controversial. More research is needed to determine the safety and efficacy of AOA techniques.
HUMAN REPRODUCTION OPEN
(2022)
Article
Chemistry, Medicinal
Junaid Kashir, Bhavesh V. V. Mistry, Lujain BuSaleh, Michail Nomikos, Sarah Almuqayyil, Raed Abu-Dawud, Nadya AlYacoub, Hamdan Hamdan, Saad AlHassan, F. Anthony Lai, Abdullah M. M. Assiri, Serdar Coskun
Summary: The application of antigen unmasking/retrieval (AUM) enhances the visualization of PLC zeta in human sperm, allowing for accurate assessment of sperm fertilization capacity.
Review
Genetics & Heredity
Veena Unnikrishnan, John Kastelic, Jacob Thundathil
Summary: In cattle, the efficiency of ICSI is hindered by failed oocyte activation post sperm injection. Research focusing on proteins like Na/K-ATPase and PLC zeta is key to improving the success rate. Enhancing the efficiency of bovine ICSI has significant implications for the cattle breeding industry.
Article
Biochemistry & Molecular Biology
Xiaopei Zhou, Zhenxing Liu, Weimin Jia, Meiqi Hou, Xianqin Zhang
Summary: This study investigates the mechanisms underlying the effects of Actl7a gene knockout on sperm acrosome formation, male infertility, and sperm-zona pellucida binding ability during fertilization. The findings suggest that Actl7a deficiency leads to malformed sperm acrosomes, male infertility, and impaired sperm-ZP binding ability. Furthermore, abnormal localization and expression of the PLCZ1 protein in misshapen sperm are identified, resulting in reduced calcium oscillations in oocytes.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Jing Dai, Tianlei Zhang, Jing Guo, Qinwei Zhou, Yifan Gu, Jue Zhang, Liang Hu, Yurong Zong, Juan Song, Shuoping Zhang, Can Dai, Fei Gong, Guangxiu Lu, Wei Zheng, Ge Lin
Summary: Genetic variations in the ACTL9 gene in male individuals have been found to cause total fertilization failure (TFF). These variations disrupt the perinuclear theca structure and affect the localization of PLCz in sperm, leading to abnormal calcium oscillations in oocytes and subsequent TFF. Overcoming TFF can be achieved through assisted oocyte activation with calcium ionophore exposure.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Mohammad Ishraq Zafar, Shi Lu, Honggang Li
Summary: The fertilizing spermatozoon is a highly specialized cell that plays a crucial role in fertilization and embryo development. PLC zeta and PAWP are main candidates as oocyte activated factors during fertilization, but their mechanisms and treatment methods still need further research and exploration.
CELL AND BIOSCIENCE
(2021)
Review
Developmental Biology
Yuhkoh Satouh
Summary: This article reports on the study of oocyte activation induced by PLCZ1 in mice, as well as the generation of PLCZ1-deficient mouse models using genome-editing techniques. The findings show that PLCZ1 deficiency in mice leads to subfertility but can be fully restored by intracytoplasmic sperm injection, indicating a PLCZ1-independent oocyte activation mechanism. These findings raise new questions in the field of sperm biology and have implications for the treatment and phenotypic interpretation of oocyte activation failure in patients.
Article
Cell Biology
Haixia Chen, Peng Li, Xiaoling Du, Yiding Zhao, Lingling Wang, Ye Tian, Xueru Song, Ling Shuai, Xiaohong Bai, Lingyi Chen
Summary: Mutation in the SEPTIN12 gene is associated with male infertility. Male mice with Septin12 knockout are infertile and have abnormal sperm, but fertility can be restored with artificial oocyte activation. Loss of PLC zeta might be the reason for failed fertilization in Septin12-deficient sperm.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Medicine, Research & Experimental
Aylin Nikshad, Afsoon Aghlmandi, Reza Safaralizadeh, Leili Aghebati-Maleki, Majid Ebrahimi Warkiani, Farhad Motavalli Khiavi, Mehdi Yousefi
Summary: According to the World Health Organization, approximately 70 million couples worldwide suffer from infertility. Research teams have integrated various scientific branches to develop therapeutic approaches, with Assisted Reproductive Technologies (ART) being a key solution. The use of microfluidic technology has shown significant progress in improving efficiency in assisted reproduction.
Review
Cell Biology
John Charles Rotondo, Carmen Lanzillotti, Chiara Mazziotta, Mauro Tognon, Fernanda Martini
Summary: Research has shown a correlation between sperm DNA methylation and male infertility, with various genes displaying differential methylation patterns in impaired spermatogenesis and reproductive dysfunction. Specifically, DNA methylation defects in MEST and H19 within imprinted genes, as well as MTHFR within non-imprinted genes, have been linked to male infertility. Further studies are needed to better understand the mechanisms affecting methylation in sperm and its impact on male infertility.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Ferran Barrachina, Kiera Ottino, Maia Lina Elizagaray, Maria Gracia Gervasi, Leona J. Tu, Styliani Markoulaki, Raul G. Spallanzani, Diane Capen, Dennis Brown, Maria Agustina Battistone
Summary: Regulatory T cells play a crucial role in maintaining the tolerogenic state of the testis and epididymis. Depletion of Tregs leads to autoimmune orchitis and epididymitis, affecting sperm production and leading to fertility defects. Understanding these immunoregulatory mechanisms could aid in the development of new treatments for male infertility and immunocontraception.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Patricia Cosme, Ana B. Rodriguez, Maria Garrido, Javier Espino
Summary: Infertility is a growing global public health concern that has socio-psychological implications for couples. Advances in reproductive medicine have led to successful treatments like assisted reproductive techniques (ART), but the search for new therapeutic tools to improve success rates is ongoing. Recent research has focused on the antioxidant properties of pineal indolamine melatonin and its role in reproductive physiology, suggesting it may be a promising agent to counteract the negative effects of oxidative stress in fertility treatments. This narrative review aims to summarize the current state of research on melatonin's importance in reproductive physiology and evaluate its potential use in ART to improve fertility success rates.
Article
Biochemistry & Molecular Biology
Rita I. Pacheco, Maria I. Cristo, Sandra I. Anjo, Andreia F. Silva, Maria Ines Sousa, Renata S. Tavares, Ana Paula Sousa, Teresa Almeida Santos, Mariana Moura-Ramos, Francisco Caramelo, Bruno Manadas, Joao Ramalho-Santos, Sandra Gomes Amaral
Summary: The global trend of rising (male) infertility is concerning. This study aimed to understand unknown origin male infertility (UOMI) by evaluating the male gamete. The study found that idiopathic (ID) patients had the worst sperm functional profile, while unexplained male infertility (UMI) patients were similar to controls. Proteomic analysis identified several differentially expressed proteins in ID and UMI samples. SACA4 and LAMB2 were identified as potential biomarkers for distinguishing ID and UMI patients.
Editorial Material
Cell Biology
Antony Galione, Lianne C. Davis, Anthony J. Morgan
Summary: LC3-lipidation is activated by mechanisms unrelated to canonical autophagy, as this study shows that lysosomal damage induced by lysosomotropic agents or oxalate leads to TFEB dephosphorylation and translocation into the nucleus which promotes the clearance of damaged lysosomes, reducing the deleterious effects of crystal nephmpathy.
Article
Cell Biology
Anthony J. Morgan, Antony Galione
Summary: Pharmacological manipulation that disrupts lysosome membrane integrity or ionic movements can inhibit store-operated calcium entry (SOCE) by uncoupling the release of calcium from the endoplasmic reticulum. Certain agents inducing lysosomal membrane permeabilization interfere with SOCE through Stim1 oligomerization and activation of Orai, while others like the K+/H+ ionophore inhibit SOCE in a Stim1-dependent manner. Other lysosomal manipulation strategies do not affect SOCE, and the effects of lysosomal agents on SOCE can be reversed by a dynamin inhibitor.
JOURNAL OF CELL SCIENCE
(2021)
Review
Cell Biology
Junaid Kashir, Ayesha Rahman Ambia, Areez Shafqat, Muhammad Raihan Sajid, Khaled AlKattan, Ahmed Yaqinuddin
Summary: This article discusses the potential occurrence of vaccine-induced thrombotic thrombocytopenia (VITT) through inflammatory reactions and the overproduction of NETs by neutrophils, with similar autoimmune mechanisms observed in HIT.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Ahmed Yaqinuddin, Ayesha Rahman Ambia, Tasnim Atef Elgazzar, Maha Bint Mishari AlSaud, Junaid Kashir
Summary: COVID-19, caused by SARS-CoV2, is a global airway disease with significant morbidity and mortality rates, particularly affecting the elderly and those with comorbidities. IVIG administration is being explored as a potential therapeutic option to reduce inflammation and improve outcomes for severe cases, drawing on its anti-inflammatory effects observed in other inflammatory conditions.
MEDICAL HYPOTHESES
(2021)
Review
Immunology
Ahmed Yaqinuddin, Areez Shafqat, Junaid Kashir, Khaled Alkattan
Summary: COVID-19 vaccines and monoclonal antibody therapies have been widely used for prevention and treatment of the disease, but the emergence of viral variants has impacted the effectiveness of these therapies. Despite challenges posed by viral variants, through continuous improvement and research, strategies are being explored to address these variants.
Review
Medicine, General & Internal
Ahmed Yaqinuddin, Muhammad Faisal Ikram, Ayesha Rahman Ambia, Raghad Alaujan, Junaid Kashir
Summary: Alzheimer's disease is a common cause of dementia characterized by cognitive decline and memory impairment due to neurodegenerative processes. Models such as animal and 3D culture models have provided significant insights into the disease pathogenesis and potential therapeutics.
JOURNAL OF HEALTH AND ALLIED SCIENCES NU
(2022)
Article
Genetics & Heredity
Serdar Coskun, Sateesh Maddirevula, Khalid Awartani, Meshael Aldeery, Wafa Qubbaj, Junaid Kashir, Fowzan S. Alkuraya
Summary: This study investigates two cases of recurrent spontaneous oocyte activation (SOA) to identify the underlying causes and potential treatments. The results show that there is no clear genetic or pathological factor causing SOA in these patients. Further research is needed to fully understand the molecular mechanisms of oocyte activation and calcium dynamics that contribute to recurrent SOA.
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2022)
Article
Cell Biology
Areez Shafqat, Junaid Kashir, Sulaiman Alsalameh, Khaled Alkattan, Ahmed Yaqinuddin
Summary: This article discusses the basis of oocyte activation deficiency and explores the role of epigenetic regulation in it. By studying the changes in DNA methylation and key pathways involved in the regulation of Ca2+ signaling, we aim to reveal the association between these epigenetic alterations and TFF. From a therapeutic perspective, if our hypothesis is confirmed, it will provide new directions for the treatment of TFF.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Immunology
Areez Shafqat, Tarek Z. Arabi, Belal N. Sabbah, Humzah S. Abdulkader, Shameel Shafqat, Adhil Razak, Junaid Kashir, Khaled Alkattan, Ahmed Yaqinuddin
Summary: The COVID-19 virus has mutated significantly, giving rise to variants of concern (VOCs) that are more transmissible and with increased ability to evade antibody responses. While COVID-19 vaccines may have reduced efficacy in preventing infection, they still offer protection against severe cases, likely due to the role of T-cell responses in maintaining immunity. Understanding T-cell responses is crucial for informing public health policies and future vaccine development.
Article
Chemistry, Medicinal
Junaid Kashir, Bhavesh V. V. Mistry, Lujain BuSaleh, Michail Nomikos, Sarah Almuqayyil, Raed Abu-Dawud, Nadya AlYacoub, Hamdan Hamdan, Saad AlHassan, F. Anthony Lai, Abdullah M. M. Assiri, Serdar Coskun
Summary: The application of antigen unmasking/retrieval (AUM) enhances the visualization of PLC zeta in human sperm, allowing for accurate assessment of sperm fertilization capacity.
Review
Cell Biology
Wjdan S. Bafleh, Haia M. R. Abdulsamad, Sally M. Al-Qaraghuli, Riwa Y. El Khatib, Rawdah Taha Elbahrawi, Azhar Mohamud Abdukadir, Shaima M. Alsawae, Zakia Dimassi, Hamdan Hamdan, Junaid Kashir
Summary: The recent COVID-19 pandemic has brought about significant changes in various fields, including society, law, economics, science, and medicine. The use of mRNA-based vaccines has been approved for the first time by drug regulatory authorities to combat the outbreak. While this represents a novel application of mRNA technology in vaccination medicine, the introduction of RNA into cells to produce molecules is not a new concept. It has been commonly practiced in research to manipulate oocytes and embryos and has potential therapeutic and diagnostic applications in combating infertility. This article describes the potential clinical applications, advantages, and limitations of mRNA-based platforms, and discusses how recent advances driven by the pandemic can benefit infertility treatment. Future directions for enhancing RNA therapeutics in reproductive biology, specifically in oocyte and embryo delivery, are also presented.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Chemistry, Medicinal
Haia M. R. Abdulsamad, Zoha F. F. Murtaza, Hessa M. M. AlMuhairi, Wjdan S. S. Bafleh, Salma A. A. AlMansoori, Shaikha A. A. AlQubaisi, Hamdan Hamdan, Junaid Kashir
Summary: Oocyte activation, driven by calcium oscillations mainly regulated by PLC zeta, is crucial for mammalian fertilization and embryogenesis. Failure of calcium release or defects in related mechanisms can lead to infertility in humans. Exploration of PLC zeta and its patterns in human sperm may offer potential for diagnosing and treating human fertility issues. This review provides a comprehensive update on the clinical associations between calcium release, PLC zeta, oocyte activation, and human fertility, discussing their implications in defective embryogenesis and infertility treatments.
Review
Obstetrics & Gynecology
Junaid Kashir, Durga Ganesh, Celine Jones, Kevin Coward
Summary: Oocyte activation deficiency (OAD) is a major cause of ICSI cycle failure. Assisted oocyte activation (AOA) is a method that artificially increases the levels of intracytoplasmic calcium ions (Ca2+) through mechanical, electrical, and/or chemical stimuli. However, the safety and efficacy of AOA are still controversial. More research is needed to determine the safety and efficacy of AOA techniques.
HUMAN REPRODUCTION OPEN
(2022)
Article
Biochemistry & Molecular Biology
Ahmed Yaqinuddin, Abdul Hakim Almakadma, Junaid Kashir
Summary: Less than 2% of children are reported to test positive for SARS-CoV-2, but increasing reports describe COVID-positive children showing symptoms resembling Kawasaki disease. The authors discussed how SARS-CoV-2 infection leads to activation of proinflammatory cytokines and the production of neutrophil and macrophage extracellular traps.
AIMS MOLECULAR SCIENCE
(2021)
Article
Andrology
Junaid Kashir, Bhavesh Mistry, Maha Adel Gumssani, Muhammad Rajab, Reema Abu-Dawas, Falah AlMohanna, Michail Nomikos, Celine Jones, Raed Abu-Dawud, Nadya Al-Yacoub, Kevin Coward, F. Anthony Lai, Abdullah M. Assiri
Summary: The study shows that with advancing male age, levels and variability of PLC zeta protein and mRNA in sperm decrease. There are also changes in the localization patterns of PLC zeta in sperm from older male mice.
ASIAN JOURNAL OF ANDROLOGY
(2021)